PVFS/ME/CFS Watch

Thursday, November 27, 2008

GW was founded in 1998 and listed on the AiM, a market of the London Stock Exchange, in June 2001. Operating under license from the UK Home Office, the company researches and develops cannabinoid pharmaceutical products for patients who suffer from a range of serious ailments, in particular pain and other neurological symptoms.

GW has assembled a team of over 100 scientists with extensive experience in developing both plant-based prescription pharmaceutical products and medicines containing controlled substances. GW occupies a world leading position in cannabinoids and has developed an extensive international network of the most prominent scientists in the field.

Here is a copy, in full, of three recent reports from the website of GW Pharmaceuticals plc

Porton Down, UK, 8 September 2008: GW Pharmaceuticals plc (GWP:AIM) announces positive results from a placebo-controlled “randomized withdrawal” study of Sativex® in patients with neuropathic pain due to Multiple Sclerosis (MS). This study design is described by regulators as being sufficient to satisfy the need for long-term efficacy data.

This randomized withdrawal study evaluated 42 MS patients with central neuropathic pain who had previously been in a Sativex Phase III MS neuropathic pain study and who continued to take Sativex on an open label basis for 12 weeks. They were then randomized to Sativex or placebo for a further 4 weeks in a double-blinded manner. During the randomized period, patients were not permitted to adjust their dose. The purpose of this blinded 4-week “randomized withdrawal” study was to assess the maintenance of pain control in patients who remain on Sativex versus those who switch to placebo.

In the patients who were randomized to Sativex pain scores remained stable. In the patients randomized to placebo, pain and sleep scores deteriorated. The prospectively defined primary efficacy endpoint of the study - the time to treatment failure - was statistically significantly in favour of Sativex (p=0.036). The difference between Sativex and placebo was also significant for mean pain score (p=0.028) and sleep quality (p=0.015). The results of all other symptom-related endpoints showed that Sativex patients maintained or improved their response whilst the symptoms of those who switched from Sativex to placebo worsened in the 4 weeks following cessation of active treatment. During the randomized withdrawal period, there were 2 patients with adverse events on Sativex, and 5 on placebo. One patient on placebo withdrew from the study. There was no evidence of any withdrawal syndrome.

Until now, all the evidence for long-term maintenance of efficacy of Sativex has come from long-term open-label exposurei. The results reported today confirm in the context of a placebo-controlled double-blind study that efficacy is indeed maintained in long-term use.

The results of this study are of further significance to GW since the design bears important similarities to the ongoing Phase III MS spasticity study requested by the UK regulator prior to granting approval for Sativex. This ongoing Phase III study involves all patients receiving Sativex for 4 weeks, following which Sativex responders are randomized to continue on Sativex or switch to placebo for a further 12 weeks. This study is due to report results in Q1 2009 with a regulatory submission targeted for H1 09.

Dr Stephen Wright, GW’s R&D Director, said: “This is the first placebo-controlled study showing that Sativex provides long term efficacy for MS patients with neuropathic pain and supplements previously published open-label studies. In addition, these results support the design of the ongoing Phase III trial in MS spasticity. It is encouraging to note that if the difference between Sativex and placebo achieved in the results today are replicated in the ongoing Phase III MS spasticity study, this Phase III study will meet its objectives.”

Porton Down, UK, 1 October 2008: GW Pharmaceuticals plc (GWP:AIM) announces that it has completed patient recruitment into its Sativex® Phase III MS Spasticity trial. This trial was requested by the UK regulator prior to obtaining approval for Sativex in this indication. The trial is due to report results in Q1 09 and a regulatory submission is planned shortly thereafter.

In total, 575 patients have been recruited into this study, by far the largest study GW has ever undertaken. Recruitment was achieved in just ten months using 52 hospital sites in five countries – UK, Spain, Italy, Czech Republic and Poland.

In December 2007, the UK regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), published a Public Information Report on Sativex which provided specific guidance on the route to approval in the indication of MS spasticity. The key outstanding requirement was to perform an additional Phase III clinical trial, the design of which was specified by the UK regulator and formally agreed in writing with GW.

The Phase III trial follows an “enriched design” which first identifies responders over a four week period (Phase A), and then focuses on analysing the effect of Sativex vs placebo on those responders over a further period of 12 weeks (Phase B). The study has enrolled 575 patients into Phase A and it is expected that approximately 255 patients will enter Phase B. This will exceed the original target number of 244 Phase B patients. The primary endpoint of the study is the difference in the severity of spasticity as assessed on the validated Numeric Rating Scale between the Sativex and placebo groups in Phase B of the study.

GW recently reported positive results from a placebo-controlled “randomized withdrawal” study of Sativex in patients with MS neuropathic pain, the design of which bears important similarities to the Phase III MS spasticity study. If the difference between Sativex and placebo achieved in the MS pain trial are replicated in the Phase III MS spasticity study, this Phase III study will meet its objectives.

Dr Stephen Wright, R&D Director, said, “This is the largest study that GW has undertaken and I am delighted that our clinical operations team has completed patient recruitment in such a rapid time frame. We look forward to reporting the results of this study and to submitting a regulatory application next year.”

"To the very few physicians still practicing today who began seeing patients with this illness some 40 years ago and who have continued to record and publish their clinical findings throughout, the current enthusiasm for renaming and reassigning this serious disability to subgroups of putative and vague 'fatigue' entities, must appear more of a marketing exercise than a rational basis for essential international research.It was not always so unnecessarily complicated!"-Dr. E. G. Dowsett-Redefinitions of ME/CFS –A 20th Century Phenomenon

Dr. E.G. Dowsett, UK microbiologist, immunologist and virologist, had an interest in hospital infections and epidemiology when she began collaborating with Dr. Melvin Ramsay on the study of ME. in 1976. Since then she has been an outspoken advocate for patients and researchers on properly distinguishing the well-defined historic disease ME from CFS. (See A Rose By Any Other Name)

In her article with Ramsay, McCartney and Bell, Myalgic Encephalomyelitis (M.E.) - A Persistent Enteroviral Infection? (abstract), Dr. Dowsett states, "In our opinion, two major errors are responsible for the present confusion surrounding the case definition, aetiology and diagnosis of M.E. First, there has been a failure to distinguish the syndrome from post-viral debility following Epstein-Barr mononucleosis, influenza and other common fevers. Compared with M.E., these lack the dramatic effect of exercise upon muscle function, the multi-system involvement, diurnal variability of symptoms and prolonged relapsing course. Laboratory tests can distinguish chronic mononucleosis and other infections which, as our results show, may occasionally co-exist with M.E. and, by their immunosuppressive effect, precipitate relapse. Second, there has been a failure to recognize the unique epidemiological pattern of M.E., which, from earliest accounts, has led to confusion with non-paralytic poliomyelitis."

Dowsett, Ramsey, McCartney and Bell Definition summary:

"Endemic prevalence alternate with periodic epidemics, showing a curious predilection for female staff of health care and teaching institutions. Maximum incidence in both sexes occurs in the third decade. M.E. is a multi-system syndrome including nervous, cardiovascular, endocrine and other involvement, distinguished by severe muscle fatigue following trivial exertion. Other characteristics include high morbidity, low mortality, a prolonged relapsing course and variation in intensity of symptoms within and between episodes, tending to chronicity."

Patient Selection

"We adopted the following clinical criteria for investigation of M.E.: a syndrome commonly initiated by respiratory and/or gastro-intestinal infection but an insidious or more dramatic onset following neurological, cardiac or endocrine disability occurs. The pathognomonic features are: a complaint of general or local muscular fatigue following minimal exertion with prolonged recovery time; neurological disturbance, especially of cognitive, autonomic and sensory functions; variable involvement of the cardiac and other systems; a prolonged relapsing course."

A coroner has accused the NHS of systemic failure after a 60-year-old woman was found dead a week after her request for an ambulance was cancelled by a doctor involved in a "cost cutting exercise".

Ruth Hedge complained of vomiting, diarrhoea, and shaking, and an ambulance was initially dispatched to her home after she called 999 and spoke to an emergency controller.

But Dr Alan Stevenson, who was working on a pilot project for the Welsh Ambulance Service NHS Trust, aimed at reducing unnecessary emergency callouts, stood it down after speaking to Mrs Hedge, an inquest heard.

Dr Stevenson advised Mrs Hedge to contact her local GP out-of-hours service instead, and told her: "I don't think an ambulance is what you need."

Mrs Hedge, a divorcee, made a number of calls but did not contact the correct service. Her body was found at her home in Borth, West Wales, a week later, after neighbours became concerned.

The Pembrokeshire Coroner Michael Howells, described the pilot scheme, no longer in operation, as a "cost-cutting exercise".He said: "There was a systemic failure by the NHS to provide full help to patients.

"If an ambulance was not needed the control room should have been able to transfer patients' calls directly to their nearest out-of-hours service.

"Alternatively they should have provided patients with the correct telephone number.

"The fact she was not given the telephone number shows the current system is flawed.

"The aim should be to remove barriers, not to create them."

Mr Howells added: "What Dr Stevenson was involved in was a cost-cutting exercise to try to reduce the costs of the ambulance service.

"This death was perhaps avoidable, and is more sad for that reason."

The inquest in Aberystwyth heard that a post-mortem examination on mother-of-one Mrs Hedge was inconclusive.

Mr Howells recorded a narrative verdict that Mrs Hedge died of natural causes, aggravated by neglect.